Heart Failure (HF) is the most frequent cause of hospitalization among patients aged 65 or greater and leads to an enormous personal, societal and economic burden for the US population. Loop diuretics such as torsemide and furosemide are a cornerstone of HF therapy utilized to improve congestive symptoms. Prior data suggest that torsemide compared to furosemide advantageously alters pathophysiological mechanisms associated with progression, has a favorable pharmacodynamic profile and may decrease HF morbidity and mortality. Yet, furosemide is overwhelmingly utilized in daily practice which highlights clinical equipoise and an unmet need for an adequately powered study to definitively determine whether torsemide compared to furosemide improves outcomes to guide clinical practice. The ToRsemide compArisoN with furoSemide FOR Management of HF (TRANSFORM-HF) trial is a robustly-powered, prospective, randomized, comparative-effectiveness study which will change guidelines and have immediate clinical implications for the management of millions of patients with HF. The primary hypothesis of the TRANSFORM-HF trial is that torsemide will reduce all-cause mortality by a relative 15% compared with furosemide over a period of 12 months. Important secondary hypotheses include that torsemide compared to furosemide will 1) reduce 1-year all-cause mortality and first HF re-hospitalization; 2) improve health-related quality of life; and 3) increase survival time and decrease total cardiovascular hospitalizations compared with furosemide. The specific aims of the TRANSFORM-HF Clinical Coordinating Center (CCC) and Data Coordinating Center (DCC) are to (1) Develop and administrate a clinical trial organization to efficiently coordinate study conduct and analysis; (2) Implement and monitor a ?real-world?, large-scale, pragmatic, clinical-effectiveness study using streamlined data acquisition with call center follow-up, and (3) Disseminate the trial results and implications to a broad audience and serve as a prototype for future pragmatic clinical trials. Our prospective, unblinded, 2-arm, phase III clinical trial of 6,000 hospitalized HF patients targeting robust enrollment of racial and ethnic minorities and women will randomize subjects 1:1 to either oral torsemide or furosemide prior to discharge. Enrollment will occur at 50 US hospital sites with established HF clinical excellence. A systematic data acquisition approach will minimize investigator and subject burden and use a call center at 6 and 12 months to document vital status, medication adherence, and health-related quality of life, and to acquire hospitalization information. The TRANSFORM-HF trial will be led by investigators and an operations team with substantial experience and expertise in HF care, clinical trials, data integration and administration working within the highly proven environment of the Duke Clinical Research Institute. This application is submitted as two clustered R01 grant proposals which detail a CCC (PI-Dr. Velazquez) and a DCC (PIs-Drs. Anstrom and Eisenstein). This proposal presents the CCC application.